The influence of high-dose intravenous immunoglobulins (HD-IVIG) on the clinical status and T4 cell count of adults with AIDS-related complex (ARC) and Walter-Reed 5 (WR5) was evaluated in a randomized double-blind longitudinal study. Inclusion criteria were: (1) T4 cells less than 400/microliters and (2a) oral thrush or cutaneous anergy or (2b) two clinical ARC criteria (fever, diarrhea, weight loss, fatigue, night sweats). Thirty patients [28 males, 2 females, median age 41 (24-64) years] with ARC (n = 8), WR5 (n = 12) and both (n = 10) were stratified according to their T4 cell count (greater than or equal to vs. less than 300/microliters). Fifteen patients received 0.4 g/kg body weight IVIG and 15 placebo (albumin 0.03%) every other week for 26 weeks with follow-up for another 26 weeks. The clinical status was defined as a score consisting of fever, diarrhea, night sweats, fatigue, weight loss, oral candidiasis and mucosal or cutaneous herpes simplex. Clinical examination and routine laboratory assessments were performed before initiation of the study and before each administration, lymphocyte phenotyping every 4 weeks and cutaneous reaction, serology and lymphocyte stimulation every 12 weeks. Both groups were comparable in initial clinical symptoms and laboratory values. Seven patients developed AIDS (treatment group: 3, placebo group: 4), 1 patient died by homicide. After 26 weeks, the clinical score (particularly fatigue and fever) was significantly improved in the treatment group, while the T4 cell count and other clinical and immunological parameters remained unaltered. This limited effect was still evident at termination of the study after 52 weeks. In conclusion, HD-IVIG can improve the clinical status of patients with advanced HIV-1 infection without obviously correcting the underlying impaired cellular immunity. The substitution of intact antibodies in the state of functional hypogammaglobulinemia is suggested as possible therapeutic mechanism.